The present application relates to a method and apparatus for monitoring blood coagulation or other reactions that alter flow characteristics of blood in vitro.
Monitoring of the ability of the blood to coagulate is critical to the diagnosis and treatment of several medical conditions. For patients taking anticoagulants, regular monitoring of blood coagulation is important in determining the course of treatment.
Coagulation of the blood occurs when the soluble plasma protein fibrinogen is converted into the insoluble polymer fibrin. This conversion is catalyzed by the proteolytic enzyme thrombin. Activation of thrombin is the endpoint of a cascade of activation reactions involving coagulation factors. Exposure of blood to a foreign surface initiates activation of coagulation factors forming the contact activation or intrinsic pathway, whilst damage to the blood vessel endothelium initiates activation of the tissue factor or extrinsic pathway. Several of the factors involved in promoting coagulation require modification by a Vitamin K dependent enzyme. Oral anticoagulants such as warfarin (Coumadin®) act by blocking the activation of Vitamin K to the form required during the synthesis of these coagulation factors.
The Prothrombin Time (PT) test is a standardized assay for evaluating the adequacy of coagulation by the tissue factor pathway. The tissue factor pathway can be activated in vitro by mixing blood with a preparation of thromboplastin (which comprises tissue factor and phospholipid). To perform a PT test, a standardized thromboplastin reagent is added to a blood or plasma sample, and the extent of coagulation as a function of time is monitored.
Devices are known in which the impedance of the blood sample is used as a measure of coagulation (for example, Jina U.S. Pat. No. 6,673,622). This method is used in the HemoSense® InRatio® PT test meter, which requires a small amount of blood (˜15 μL), delivers a PT test result within several minutes, and is suitable for home or clinical use. However, impedance measurement of the blood sample produces a small signal, which may lead to error in determination of coagulation onset. Furthermore, impedance measurement relies on detecting a change in the electrical properties of the blood upon coagulation rather than mechanical changes in the blood. Changes in the electrical properties of coagulating blood are complex and therefore it is difficult to extract a reliable indicator of coagulation. Since coagulation is a mechanical change to the blood, making a measurement of the mechanical properties of the blood is a more direct and accurate way of determining coagulation.
Other examples of electrochemical devices for monitoring of blood coagulation are disclosed in US Patent Publication 2004/0072357, and U.S. Pat. Nos. 6,046,051, 6,066,504, 6,338,821, 6,620,310, 6,673,622, and 3,699,437.